Smart Release Skin Patch Corrects Type II Diabetes in Model

Exendin-4 (Ex4) is a hormone first isolated in 1992 from the saliva of the Gila monster (Heloderma suspectum). It is a 39-amino-acid peptide, which induces secretion of insulin with glucoregulatory effects. Ex4 increases insulin secretion in response to eating meals; the result is the release of a higher, more appropriate amount of insulin that helps lower the rise in blood sugar from eating. Once blood sugar levels decrease closer to normal values, the pancreatic response to produce insulin is reduced. Synthetic Ex4 (Exenatide) was approved by the [U.S.] Food and Drug Administration in 2005 for patients whose diabetes was not well controlled by other oral medication.

Investigators at the [U.S.] National Institute of Biomedical Imaging and Bioengineering (Bethesda, MD, USA) recently described a novel way to deliver Ex4 as part of a bimodal therapeutic approach to treat type II diabetes. The investigators immobilized and stabilized Ex4 by integrating it into mineral particles composed of calcium phosphate. A second drug compound, the enzyme glucose oxidase (GOx), was similarly immobilized in particles composed of copper phosphate. Both mineral complexes were loaded into a patch containing alginate microneedles.

The microneedle patch concept was tested in a diabetes mouse model. After application, the needles released the mineral complexes through the skin. When blood sugar was elevated beyond a precise point, reaction with copper phosphate and glucose oxidase produced slight acidity, which caused calcium phosphate to release some Ex4. Rising glucose levels triggered the release of Ex4, which induced insulin secretion to reduce the glucose level, which in turn reduced and stopped Ex4 release. As an added bonus, integration of mineralized particles enhanced the mechanical strength of the alginate-based microneedles by crosslinking to facilitate skin penetration.

Results published in the November 26, 2017, online edition of the journal Nature Communications revealed that a patch about half an inch square contained sufficient drug to control blood sugar levels in mice for a week.

“That is why we call it responsive, or smart release,” said senior author Dr. Xiaoyuan Chen, senior investigator in the laboratory of molecular imaging and nanomedicine at the National Institutes of Health. “Most current approaches involve constant release. Our approach creates a wave of fast release when needed and then slows or even stops the release when the glucose level is stable. Diabetes is a very serious disease and affects a lot of people. Everybody is looking for a long-acting formula.”

Related Links:
National Institute of Biomedical Imaging and Bioengineering